Level 2 Remember DNA more stable than RNA

Level 2

Remember… *DNA more stable than RNA • * All organisms must be able to reproduce to keep life going CELL DIVISION

One cell becoming two

All Reproducing Cells � 1. Replicate DNA in parent cell during the S phase. � 2. Replicate organelles � 3. Perform cytokinesis- division of cytoplasm and cell membrane. �Cyto – cell, kinesis- movement

Reasons for Cell Division In unicellular organisms it is primarily for reproduction of themselves. � In multicellular organisms it is for reproduction, growth, and repair of tissues. � If cells do not divide, they get to big. � Two major problems with big cells: � �DNA cannot code for all of the necessary functions �Substances cannot enter and exit fast enough.

Figure 9. 3 The Eukaryotic Cell Cycle Cytokinesis Preparing for mitosis S phase- Commitment to cell division

Three Reasons for Cell Division

Four Events that Must occur for Cell Division A reproductive signal (intracellular/extracellular) to initiate division. � Replication of DNA, so the new cells match identically to old cell. � Segregation- process by which DNA is passed to each of the two resulting new cells. � Cytokinesis- process by which the cell membrane and cell wall separate into two new cells. �

Binary Fission � In prokaryotes, the entire single-celled organism divides. � First it doubles in size, then duplicates its DNA, and then divides. � In prokaryotes, the initiating reproductive signal is thought to be environmental conditions and food supply

DNA Replication in Prokaryotes (S phase) � Most prokaryotes only have one chromosome, and it is circular. � Circular chromosomes are also in chloroplasts, mitochondria, and viruses. � ori- origin site of DNA replication � ter- terminus of DNA replication

Figure 9. 2 Prokaryotic Cell Division (Part 1)

Prokaryotic DNA Replication � Referred to as circular or theta replication. � Cleavage furrow follows after replication � The two resulting cells are clones= identical cells. � Mitosis is thought to have evolved from binary fission…commonality: synthesis and division

Eukaryotic Cell Division � Most complex eukaryotes originate from a single cell: fertilized egg. � The formation of a multicellular organism from a fertilized egg is known as development. � Eukaryotic cell division are driven by the needs of the organism, not the environmental conditions and food supply.

Somatic cells vs. Germ cells The egg surrounded by sperm.

Eukaryotic Cell Division � Eukaryotic cells also have more chromosomes to duplicate. � Eukaryotes have a nucleus that needs to divide before cytokinesis can take place. This is called mitosis. � Mitosis is the division of the nucleus. � Cytokinesis is the division of everything but the nuclear contents. Different in plants than animals

Control of Mitosis in Eukaryotes � Cell cycle- the events that occur to produce two eukaryotic cells from one. � Cell cycle has two main phases: Interphase 90 -95% of time, Mitosis 5% of time. � Cell types vary with how long they live in interphase. � Mitosis and cytokinesis are referred to as the M phase of the cell cycle, but cytokinesis always follows mitosis.

DNA Division � Genome- term for all genetic material in a cell. � In humans the genome is 7 ft. /cell � DNA has 2 appearances: �Chromatin �Chromosome

Somatic Cells vs. Germ Cells � � � Perform mitosis Parent cell 2 identical daughter cells 1 division following S phase 2 n or diploid Humans =46 � � � Somatic Cells Perform meiosis Germ cell 4 non-id. Cells 2 divisions following S phase n or haploid Makes gametes: egg/ sperm Humans =23 Germ Cells

Data Set Question 1 U 3, D 1

Remember cell movement… � Cytoskeleton is composed of microtubules, microfilaments, and intermediate filaments. � Centrioles are a part of cytoskeleton made of microtubules. � Microtubules also make up spindle fibers � Proteins will also move things

Centrioles

Interphase

Cell Cycle � G 1 - first growth, everyday activity, first checkpoint will be passed…point of no return. � S- DNA replicates, (46 -92 in humans: 4 n) � G 2 - second growth, second checkpoint where all DNA is proofed and organelles checked for cell division.

Mitosis � Mitosis is the segregation step (3) for eukaryotic cells. � Sister chromatids = replicated DNA. � Chromatids held together by cohesionprotein complex, found at centromere.

Before and after the S phase

Figure 9. 7 Chromosomes, Chromatids, and Chromatin

Histones Web-like proteins that have a positive charge, and interact with the negative phosphates of DNA. � Histones form nucleosomes. � �Eight histone molecules. � 146 base pairs of DNA �Histone One H 1. Clamps DNA to histone core. � Chromatin will condense until chromatids move apart in anaphase.

Figure 9. 8 DNA is Packed into a Mitotic Chromosome (Part 1)

Centrosomes � Centrosomes consist of a pair of centrioles. Centrioles are hollow tubes consisting of nine microtubules. Each centriole pair is situated perpendicular to one another. � At G 2 M phase, the centrosomes migrate to opposite ends of the cell. � Plant cells do not have centrosomes, just have a microtubule organization center.

MITOSIS IS DIVISION OF THE NUCLEUS MITOSIS ANIMATION MITOSIS-GOOD ANIMATION

Interphase cell (Look at the chromatin in the blue nucleus and the yellow cytoskeleton. )

Mitosis Step 1: Prophase � Nuclear membrane begins to break down � Cohesion proteins are removed from chromatin, except at centromere, and the chromatids become distinctly visible. � Kinetochores (proteins) develop at centromere region � Microtubules extend from centrioles, forming spindle fibers.

Cell in Prophase

Prometaphase � Not officially step two. � Nuclear membrane completely disappears, as well as nucleolus

Figure 9. 10 Mitosis (Part 1)

Metaphase � This is when all the centromere are in the middle of the cell at the equatorial plate. � Chromosomes are maximally condensed at this phase. � At the end of metaphase all chromatid pairs will separate simultaneously. This is the third checkpoint.

Cell in Metaphase

Anaphase Sister chromatids begin to separate. Sister chromatids separate into sister chromosomes. � Separation of chromatids is accomplished by a protease called separase hydrolyzing the cohesion proteins at the centromere. � Separase is controlled by a competetive inhibitor. � Spindle Checkpoint- when all kinetochores are attached to s. f. then separase becomes activated. � �

Cell in Anaphase

Figure 9. 11 Chromatid Attachment and Separation

Anaphase � Movement of sister chromosomes away from one another is accomplished in two ways. � 1. Daughter chromosomes will propel themselves towards opposite centrosome poles (ATP ADP) � 2. Spindle fibers will shorten drawing the sister chromosomes to opposite ends of the cell. � This process takes ~10 min. to one hour.

Telophase � When sister chromosomes stop moving, the cell enters telophase. � Spindle fibers begin to break down and reform the nuclei. � Nuclear membranes and nucleoli reform around the two sets of DNA. � Mitosis is complete (segregation of DNA accomplished)

Cell in Telophase and starting Cytokinesis

Figure 9. 10 Mitosis (Part 2)

Cytokinesis The end of telophase is two nuclei in one cell; therefore, the cell needs to divide. � Cytokinesis is the process of cytoplasm division. � Animal cells divide by the cell membrane furrowing. Contraction of actin and myosin microfilaments. � Plant cells’ vesicles from the Golgi bodies, move to equatorial plate, fuse to form new C. M. Vesicle contents also create a cell plate, which becomes new cell wall. �

Figure 9. 12 Cytokinesis Differs in Animal and Plant Cells

Cell Cycle REGULATION � Critical for normal growth and development � Controlled by proteins called cyclins. � 3 Checkpoints:

Compare the difference between Theta and Eukaryotic Division � Gene # � Gene Combinations � Linking Genes � Species Variation � Inheritance from parents

Cyclins and Proteins trigger Cell Division � Cyclin- protein that causes G 1 S G 2 transition. (s phase to anaphase [inc. ]) � Kinase is an enzyme that turn on cell processes � Cyclin + Kinase = Cdk aka MPF �MPF-Maturation Promoting Factor

G Cdk G 2 checkpoint MPF Cdk ion Cyclin is degraded M Degraded cyclin accumulat Cyc S 1 . Cyclin Molecular mechanisms that help regulate the cell cycle

Figure 9. 6 Cyclin-Dependent Kinases and Cyclins Trigger Transitions in the Cell Cycle Restriction Point- once RB protein is phosphorylated, it is inactivated and cell cycle progresses.

Tumor Suppressors � � � Cancer is the result of uncontrolled cell division. When Cdk controls are disrupted cell division can ensue and not be controlled. Proteins can bind to the Cdks along the cell cycle and prevent division. These proteins are known as tumor suppressors. If these proteins are absent cancer can result. Cancer can also result because these cells do not abide by external signals: density-dependent inhibition and anchorage dependence.

Density Dependence Inhibition& Anchorage Dependence � DDI- when cells touch each other they stop dividing. � AD- cells must connect to connective tissue to divide

. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). Normal mammalian cells 25 µm

. Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells

Cancer Cells � Do not exhibit DDI or AD � Cancer cells are immortal as long as oxygenated blood is flowing. Performs angiogenesis � Telomerase creates cyclins, and with no checkpoints the cells divide unstoppably.

Cancer Terms � “onco” � Tumor � Benign � Malignant � Metastasis � Cancer Naming � Cancer causes- weak genes, environ. , lifestyle, virus (HPV)

Malignant cancer cells from the breast (See the ABNORMAL “crab” shape of the cells. )

Cancer Genes ○ RAS gene (30% of all cancers are the result of this gene mutation. ) �These are involved in normal cell to cell communication. �The cell CANNOT shutdown the signal to grow going to nucleus; so it reproduces very quickly and constantly. ○ p 53 gene (A. K. A the Guardian Angel gene. ) 50% of all cancers are the result of this mutating. �This affects a tumor suppressing gene.

� CANCER IS AN ACCUMULATION OF MUTATIONS OVER A LIFE TIME. ○ Life style vs. Genetic Predisposition. We ALL have oncogenes in our genome. Some individuals have stronger control mechanisms that resist mutations; some have weaker. Our CHOICE in life style determines HOW much or WHAT kinds of carcinogens or mutagens we expose our bodies to. � �

Data Set Question 2 (U 3, D 3)

Cell Death: Necrosis vs. Apoptosis Programmed cell death � Due to cell is unneeded, or cell is aging and may be prone to genetic damage leading to cancer. � Cell death due to damage by toxins, O 2 deprivation, or nutrient deficiency. � Cells usually swell and burst. � This usually causes inflammation due to the cell contents in the extracellular matrix Necrosis Apoptosis �

Apoptosis 1. Cell isolates itself from its neighbors 2. The chromatin is cut up into nucleosome -sized pieces. � 3. Cell forms membranous lobes that are called “blebs”. � These blebs are ingested by other cells. � Apoptosis can be intracellularly/extracellularly signaled � Caspases are used to break down cell components � Cancer drugs focus on apoptosis signals � �

Apoptosis Horror Flick � Another Exciting Apoptosis Flick �

Asexual Reproduction � Common in unicellular organisms, and some multicellular organisms such as plants. � Asexual reproduction is also known as vegetative reproduction � Asexual reproduction results in clones. Because they are identical to parents unless a genetic mutation occurs.

Sexual Reproduction � Offspring dissimilar from parents. � Gametes created by meiosis are genetically different, thus creating unique offspring. � Meiosis is the raw material basis for natural selection and evolution. (Think offspring comparison of adaptation) � Meiosis is the process of gamete formation.

Fertilization � When two haploid gametes fuse to form a zygote (new organism). � Haploid gametes = sperm + egg

Tenets of Sexual Reproduction � 1. Two parents each contribute a gamete (one chromosome set) to offspring through process of meiosis. � 2. Gametes are haploid. � Gametes called sperm and egg fuse to form a zygote (diploid).

Figure 9. 14 Fertilization and Meiosis Alternate in Sexual Reproduction (Part 1)

Figure 9. 14 Fertilization and Meiosis Alternate in Sexual Reproduction (Part 2)

Figure 9. 14 Fertilization and Meiosis Alternate in Sexual Reproduction (Part 3)

What is the purpose of mitosis? � What is the purpose of meiosis? �

Figure 9. 15 The Human Karyotype DNA chromatin in Interphase in cell. Chromosomes have been stained in Metaphase to distinguish homologous chromsomes.

Chromosome Terminology As a human you have 46 chromosomes in your somatic cells. � 23 from dad, 23 from mom. � You only have 23 chromosomes in your sex cells (egg/sperm). �

Homologous Chromosomes Each of the 23 chromosomes inherited by your parents line up in pairs. � These pairs are known as homologous chromosomes. � These homologous chromosomes are identical in size, shape, and location of genes. �

Meiosis Animation � Meiosis Simulation �

Meiosis I During Prophase I, a process called synapsis/ chiasmata occurs. Homologous chromosomes pair by adhering at their lengths. � Proteins aid in this adhesion by forming a scaffold called a synaptonemal complex. � The four bound chromatids form a tetrad. � How many chromatids are in human cells during Meiosis I? � 92 �

Meiosis I and Meiosis II Homologues will meet and � Prophase, Metaphase and form a tetrad. Anaphase similar to Mitosis and Meiosis I. � Crossing over occurs: allele swapping. � Telophase II results in four haploid daughter cells. � Telophase I- two new cells with one homologue per � One chromatid per cell (still replicated chromatids) �

Meiosis I � The chromatids that result are known as recombinant chromatids � Not all organisms directly enter Meiosis II. � If an organism does not, it does form a nuclear membrane at the end of Telophase I � Telophase I is followed by interkinesis, which is similar to mitotic interphase

Meiosis II � Homologues are not identical like in Meiosis I because of crossing over. � The result is four haploid nuclei, with a single set of unreplicated chromosomes.

So what causes genetic diversity Synapsis, crossing over, and segregation of homologues � Aneuploidy- when there are either missing or excessive chromosomes. � �Monosomy �Trisomy 10 -30% human zygotes show trisomy � Aneuploidy, ~20% of miscarriages due to aneuploidy (extra or missing chromosomes) �Polyploidy complete extra sets of chromosomes, can occur naturally, can be result of genetic engineering �Aneuploidy Simulations- Utah Site

Cell Signaling…Remember � Glycolipids and Glycoproteins � Each molecules has its own distinct shape � ECM interacts with cells

If cells don’t‘ communicate with one another they will not function and eventually die.

Cells communicate via chemicals

3 Types of Cell Communication � 1. Direct- physical contact between cells � 2. Local- grwoth factors released into a local area, or neuron synapses. (no direct contact) � 3. Long Distance- hormones and phermones

Direct Contact

Local and Long Distance within an organism.

Phermones

Signal Transduction Pathway � 1971, Earl Sutherland, Vanderbilt U. � 1. RECEPTION � 2. TRANSDUCTION � 3. RESPONSE

� 1. RECEPTION- molecule binds to cell membrane. � 2. TRANSDUCTION- occurs in cytoplasm/nucleus. Changes signal into something usable. � 3. RESPONSE- usually involves DNA making protein. Turns signal into action

Step 3: Response

Signal Transduction � The phone call…

SEE THE CONFORMATI ON SHAPE CHANGE BY THE RECEPTOR PROTEIN CAUSED BY THE LIGAND BINDING. Signal molecule (ligand) Gate closed Ligand-gated ion channel receptor Ions Plasma membrane Gate open Cellular response Gate closed

Enzyme Review � Substrate � Active Site � Enzyme � Competitive Inhibitor � Non-competitive Inhibitor � Ase � Negative Feedback Inhibition

Signal Transduction Pathways � 1. G Protein Linked Receptors � 2. Tyrosine Kinase � 3. Ion Channel Receptors � 4. Intracellular Receptors

G Protein Linked Receptors � On cell membrane, of ALL CELLS. � Ligand binds=conformational shape change � G proteins usually phosphorylate things to activate them.

G protein Receptor

Tyrosine Kinase Used in emergency growth/repair situations � Activates many proteins simultaneously �

Ion Channel Receptors � Aka Ligand Gated Ion Channels

Intracellular Receptors Usually for hormones or steroids. � Lipid based so diffuse through c. m. � Aka transcription factors because they make m. RNA �

Secondary Messengers In cytoplasm � Take message from c. m. and relay it to somewhere in cell. � Common in muscle contractions � e. g. c. AMP �

First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP c. AMP Second messenger Protein kinase A Cellular responses

Receptor protein

Cascades � Cacade = Amplification… 1 becomes 2, 2 to 4, 4 to 8…E Conservation � Protein Kinase Cascades turns ON processes by phosphorylating � Protein Phosphotase Cascades turn OFF by dephosphorylating

Small signal produces a BIG response

THE BIG PICTURE Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active transcription factor P Response DNA Gene NUCLEUS m. RNA

Autosomes vs. Sex Chromosomes � Autosomes- chromosomes that codes for all traits except gender. � Homologous pairs #1 -22 � Sex chromosomes- chromosomes that code for gender. � Homologous pair #23

Mendel Father of Genetics � Experimented with pea plants � He used “truebreeding” plants which were selfpollinating. (identical offspring. ) �

Mendel and His Peas Mendel cross-bred pea plants. � Cut off the male parts (pollen), and dusted pollen from another plant to cause fertilization. (aka cross-pollination). �

Mendel studied seven different traits. � Trait- specific characteristic, like flower color. � P generation- parent generation. � F 1 generation- offspring of the P generation. � Traits are controlled by genes. � Genes- segment of DNA � Allele- different forms of a particular gene � �Ex. Hair color, eye color, plant flower color.

Segregation Mendel wanted to see if recessive traits disappeared in F 1 generation. So he crossed them to make an F 2 generation. � He realized that gametes (egg or sperm) only contain one set of genes. � These alleles segregate. � GENES SEPARATE �

Law of Independent Assortment � Just because you have one dominant gene, does not mean all of your genes are dominant. � INHERITED INDEPENDENTLY

Probability The odds that a particular event is going to take place. � If you flip a coin, there is a ½ chance/ probability that it will land on heads. � Apply this concept to segregation of alleles. �

Probability and Segregation These principles can only be viewed if there are hundreds or thousands of offspring. � You and your siblings are not enough to prove or disprove this principle. �

Allele Types � Dominant- characterized by a capital letter. � This form will be expressed if present. � Recessive- characterized by a lower case letter. � This form will only be expressed if two recessive alleles are present.

Homozygous vs. Heterozygous � Heterozygous: for a particular trait the individual has one dominant and one recessive allele. (Tt) � Homozygous: for a particular trait the individual has both dominant or both recessive alleles. (TT, tt)

Exploring Classroom Genetics Trait Pics. Trait Tongue-Rolling (R) Free Earlobe (F) Widow’s Peak (W) Straight Thumb (N) Straight Little Finger (S) Left over Right Thumb Crossing (L) Chin Cleft (C) Mid-digital Hair (H) Six Fingers (F) Phenotype- what you look like Genotype- genetic makeup that makes up phenotype

Punnett Squares � Used to predict possible offspring outcomes. � Cross one parent with another. �Tall (TT) x short (tt) �Use a Punnett Square for Rr. Yy x Rr. Yy

Dihybrid Cross

Pedigree � A chart that shows the phenotypes for an organism and all of its ancestors.

Pedigree � � � Squares=males Circles=Females Each generation is denoted by a roman numeral. Each individual is numbered in the generation Blood relations are linked by lines.

Karyotype Map of an individual’s chromosomes that have been inherited from one’s mother and father. � Cannot see chromatids, but they are present. � Specific nucleotide sequence allows dying on individual chromosomes. �

Figure 9. 15 The Human Karyotype DNA chromatin in Interphase in cell. Chromosomes have been stained in Metaphase to distinguish homologous chromsomes.

EOC L 2

11 -26 -12 � 1. List the 3 Sexual Life Cycles. � 2. Haploid vs. Diploid � 3. Somatic vs. Sex Cell � 4. Centromere…Centriole…Centrosome

Hardy Weinberg Equilibrium � 1908 proposed that the frequency of alleles/genotypes will remain constant if… � 1. A large breeding population � 2. Random mating vs. selective mating � 3. No change in allelic frequency due to mutation � 4. No immigration or emigration � 5. No natural selection

H-W Equilibrium p = the frequency of the dominant allele q = the frequency of the recessive allele � For a population in genetic equilibrium: p + q = 1. 0 (The sum of the frequencies of both alleles is 100%. ) � (p + q)2 = 1 � so � p 2 + 2 pq + q 2 = 1 The three terms of this binomial expansion indicate the frequencies of the three genotypes: � p 2 = (homozygous dominant) 2 pq = (heterozygous) q 2 = (homozygous recessive) �